Hyperbaric Oxygen Therapy - Medical Policy Manual
←
→
Page content transcription
If your browser does not render page correctly, please read the page content below
Medical Policy Manual Medicine, Policy No. 14
Hyperbaric Oxygen Therapy
Effective: April 1, 2021
Next Review: September 2021
Last Review: November 2020
IMPORTANT REMINDER
Medical Policies are developed to provide guidance for members and providers regarding coverage in
accordance with contract terms. Benefit determinations are based in all cases on the applicable contract
language. To the extent there may be any conflict between the Medical Policy and contract language, the contract
language takes precedence.
PLEASE NOTE: Contracts exclude from coverage, among other things, services or procedures that are
considered investigational or cosmetic. Providers may bill members for services or procedures that are
considered investigational or cosmetic. Providers are encouraged to inform members before rendering such
services that the members are likely to be financially responsible for the cost of these services.
DESCRIPTION
Hyperbaric oxygen therapy (HBOT) is a technique of delivering higher pressures of oxygen to
the tissues. Two methods of administration are available, systemic and topical.
MEDICAL POLICY CRITERIA
I. Systemic hyperbaric oxygen therapy may be considered medically necessary when
both of the following criteria (A. and B.) are met:
A. Systemic hyperbaric oxygen therapy services must comply with the following
guidelines which are consistent with the Undersea and Hyperbaric Medical
Society criteria:
1. Patient must breathe 100% oxygen intermittently or continuously while the
pressure of the treatment chamber is increased above one atmosphere
absolute; and
2. Systemic hyperbaric oxygen pressurization should be at least 1.4
atmospheres absolute (atm abs) (20.5 psi); and
3. Treatment is provided in a hospital or clinic setting; and
B. Treatment meets one or more of the following conditions:
MED14 | 11. Acute carbon monoxide poisoning (Recommended treatment review
threshold: 5 treatments); or
2. Acute traumatic ischemia (Recommended treatment review threshold:
Reperfusion injury – 1 treatment; Crush injury – 12 treatments (3 times per
day for 2 days, then twice a day for 2 days, then daily for 2 days);
Compartment syndrome – 3 treatments (twice a day for 1 day, then 1
treatment on day 2); or
3. Chronic refractory osteomyelitis (Recommended treatment review threshold:
40 treatments); or
4. Cyanide poisoning, acute (Recommended treatment review threshold: 5
treatments); or
5. Decompression sickness (Recommended treatment review threshold: 10
treatments); or
6. Gas or air embolism, acute (Recommended treatment review threshold: 10
treatments); or
7. Gas gangrene (i.e., clostridial myositis and myonecrosis; *Recommended
treatment review threshold: 10 treatments); or
8. Non-healing diabetic wounds of the lower extremities as an adjunct to ongoing
conventional wound care in patients who meet all of the following Criteria (a.
– c.) (Recommended treatment review threshold: 30 treatments (one or two
treatments daily):
a. Patient has type I or type II diabetes and has a lower extremity wound
that is due to diabetes; and
b. Patient has a wound classified as Wagner grade 3 or higher (see Policy
Guidelines); and
c. Patient has no measurable signs of healing after 30 days of an adequate
course of standard wound therapy including all of the following:
i. Assessment of vascular status and correction of any vascular
problems in the affected limb if possible; and
ii. Optimal glycemic control; and
iii. Optimal nutritional status; and
iv. Topical wound treatment (eg, saline, hydrogels, hydrocolloids,
alginates) with maintenance of a clean, moist bed of granulation
tissue; and
v. Debridement to remove devitalized tissue, any technique; and
vi. Pressure reduction or offloading; and
vii. Treatment to resolve infection (e.g., antibiotics); or
9. Pre- and post-treatment for patients undergoing dental surgery (non-implant-
related) of an irradiated jaw; or
10. Profound anemia with exceptional blood loss: only when blood transfusion is
impossible or must be delayed (Recommended treatment review threshold:
MED14 | 2HBOT should be continued with taper of both time and frequency until red
blood cells have been satisfactorily replaced by patient regeneration or the
patient can undergo transfusion.); or
11. Soft-tissue radiation necrosis (e.g., radiation enteritis, cystitis, proctitis) and
osteoradionecrosis (Recommended treatment review threshold for mandibular
osteoradionecrosis: 60 treatments); or
12. Idiopathic Sudden Sensorineural Hearing Loss of greater than or equal to 41
decibels and an onset of treatment within 14 days (Recommended treatment
review threshold: 20 treatments.); or
13. Necrotizing soft tissue infections; or
14. Actinomycosis; or
15. Central retinal artery occlusion; or
16. Compromised skin grafts and flaps where hypoxia or decreased perfusion has
compromised viability acutely (Recommended treatment review threshold: 30
treatments.)
II. Systemic hyperbaric oxygen for non-healing diabetic wounds of the lower extremities
as an adjunct to conventional wound care is considered not medically necessary
when Criterion I.B.8 is not met.
III. Systemic hyperbaric oxygen therapy is considered investigational for all other
indications including but not limited to other ophthalmologic conditions, non-diabetic
wounds, and acute thermal burns.
IV. Topical hyperbaric and topical normobaric oxygen therapies are considered
investigational.
NOTE: A summary of the supporting rationale for the policy criteria is at the end of the policy.
POLICY GUIDELINES
WAGNER CLASSIFICATION
• Grade 0: No open lesion
• Grade 1: Superficial ulcer without penetration to deeper layers
• Grade 2: Ulcer penetrates to tendon, bone, or joint
• Grade 3: Lesion has penetrated deeper than grade 2 and there is abscess,
osteomyelitis, pyarthrosis, plantar space abscess, or infection of the tendon and tendon
sheaths
• Grade 4: Wet or dry gangrene in the toes or forefoot
• Grade 5: Gangrene involves the whole foot or such a percentage that no local
procedures are possible and amputation (at least at the below the knee level) is
indicated
MED14 | 3LIST OF INFORMATION NEEDED FOR REVIEW
It is critical that the list of information below is submitted for review to determine if the policy
criteria are met. If any of these items are not submitted, it could impact our review and decision
outcome.
• History and physical/chart notes
• Indication for the requested service including type of HBOT planned
• Treatment plan including the following:
o Percent of oxygen that the patient will breathe while receiving therapy
o Pressurization (atm abs, psi)
o Treatment setting
• Condition being treated including how many treatments being requested
o If a diabetic wound is being treated then the request must include the following:
Type of diabetes
Location of wound
Wagner Classification
Measurable signs of healing following standard wound therapy including therapy
length of time with documentation of the following:
▬ Vascular assessment and correction, if possible, of vascular problems to
affected area
▬ Glycemic data for patient (e.g., A1C)
▬ Nutritional status
▬ Topical wound treatments utilized including wound bed description
▬ Debridement
▬ Pressure reduction or offloading
▬ Any infection treatment utilized
o If dental surgery, include description and diagnosis
o If anemia, include blood loss and ability to transfuse patient
o If necrosis, include type
o If idiopathic sudden sensorineural hearing loss, include decibels of loss and onset of
treatment
CROSS REFERENCES
None
BACKGROUND
SYSTEMIC HBOT
In systemic or large chamber hyperbaric oxygen, the patient is entirely enclosed in a pressure
chamber and breathes oxygen at a pressure greater than 1 atmosphere (atm, the pressure of
oxygen at sea level). Thus, this technique relies on systemic circulation to deliver highly
oxygenated blood to the target site, typically a wound. In addition, systemic hyperbaric oxygen
therapy can be used to treat systemic illness, such as air or gas embolism, carbon monoxide
poisoning, clostridial gas gangrene, etc. Treatment may be carried out either in a monoplace
chamber pressurized with pure oxygen or in a larger, multiplace chamber pressurized with
compressed air, in which case the patient receives pure oxygen by mask, head tent, or
endotracheal tube.
MED14 | 4Mild Hyperbaric Oxygen Therapy
Oxygen therapy delivered via soft-sided chambers is referred to as mild hyperbaric oxygen
therapy. While this implies that these chambers provide HBOT, the therapy is not considered
hyperbaric as they provide pressurization of only about 4.5 psi, compared with true HBOT
which is defined as pressurization of 20.5 psi or higher.
TOPICAL OXYGEN THERAPY
Topical Hyperbaric Oxygen Therapy
Topical hyperbaric oxygen therapy is a technique of delivering 100% oxygen directly to an
open, moist wound at a pressure slightly higher than atmospheric pressure. It is hypothesized
that the high concentrations of oxygen diffuse directly into the wound to increase the local
cellular oxygen tension, which in turn promotes wound healing. This therapy has been
investigated as a treatment of skin ulcerations resulting from diabetes, venous stasis,
postsurgical infection, gangrenous lesion, decubitus ulcers, amputations, skin graft, burns, or
frostbite.
Topical hyperbaric oxygen devices consist of an appliance to enclose the wound area
(frequently an extremity) and a source of oxygen; conventional oxygen tanks may be used.
Topical hyperbaric oxygen therapy may be performed in the office, clinic, or may be self-
administered by well-trained patients in the home. Typically, the therapy is offered for 90
minutes per day for 4 consecutive days. After a 3-day break, the cycle may be repeated. The
regimen may last for 8 to 10 weeks.
Topical Normobaric Oxygen Therapy
Devices that deliver topical oxygen to a wound at normal atmospheric pressure (normobaric)
are not considered hyperbaric oxygen therapy. These devices may also be called low dose
tissue oxygenation systems. An example of a normobaric oxygen delivery system is the
TransCu O2™, a small handheld device with an attached cannula. According to the
manufacturer, the TransCu O2 is “intended for use with wound dressings to treat the following:
skin ulcerations due to diabetes, venous stasis, post-surgical infections and gangrenous
lesions; pressure ulcers; infected residual limbs; skin grafts; burns; and frostbite.” The device
concentrates room air to 99.9% oxygen which is delivered via the cannula which is placed
under the wound dressing.
REGULATORY STATUS
In 2013, U.S. Food and Drug Administration (FDA) published a statement warning that non-
FDA approved uses of HBOT may endanger the health of patients.[1] “Patients may incorrectly
believe that these devices have been proven safe and effective for uses not cleared by FDA,
which may cause them to delay or forgo proven medical therapies. In doing so, they may
experience a lack of improvement and/or worsening of their existing condition(s).”
The following are examples of oxygen therapy devices:
In February 1999, the Numobag™ Kit (Numotech, Inc) for application of topical hyperbaric
therapy was cleared for marketing by the FDA through the 510(k) process. The FDA
determined that this device was substantially equivalent to existing devices. Another
example is the AOTI Hyper-Box™ (AOTI Ltd., Galway, Ireland) which was cleared by FDA
MED14 | 5in 2008.
In August 2009, the TransCu O2 (Electrochemical Oxygen Concepts, Inc.) was cleared for
marketing by the FDA through the 510(k) process as substantially equivalent to existing
devices.
There are numerous FDA-approved hyperbaric oxygen chambers. In May 2005, the ATA
Monoplace Hyperbaric System (ATA Hyperbaric Chamber Manufacturing, Inc.) was cleared for
marketing by the FDA through the 510(k) process. The FDA determined that this device was
substantially equivalent to existing hyperbaric devices.
EVIDENCE SUMMARY
Current evidence is sufficient to determine the effectiveness of hyperbaric oxygen therapy
(HBOT) for the indications that meet the above medical necessity criteria. Assessing the
effectiveness and safety of HBOT for the investigational indications requires randomized
controlled trials comparing HBOT with the conventional treatments for each indication.
Therefore, the following literature review on HBOT focuses on randomized controlled trials
(RCTs) and systematic reviews of RCTs for the investigational indications.
Assessment of efficacy for therapeutic interventions involves a determination of whether the
intervention improves health outcomes. The optimal study design for a therapeutic intervention
is a randomized controlled trial (RCT) that includes clinically relevant measures of health
outcomes. Intermediate outcome measures, also known as surrogate outcome measures, may
also be adequate if there is an established link between the intermediate outcome and true
health outcomes. When the primary outcomes are subjective (e.g., pain, depression), sham-
controlled RCTs are needed to assess the effect of the intervention beyond that of a placebo
effect.
TOPICAL HYPERBARIC OXYGEN
Due to their different methods of delivery, topical and systemic hyperbaric oxygen are distinct
technologies such that they must be examined separately.[2] There is minimal published
literature regarding topical hyperbaric oxygen therapy. A 2015 Cochrane review of
interventions for treating gas gangrene evaluated the safety and efficacy topical HBOT and
Chinese herbs as treatments options.[3] Re-analysis if cure rate did not show beneficial effects
from either treatment. In 1984, Heng published a controlled study of topical hyperbaric oxygen
therapy in 6 patients with 27 ulcers compared to no treatment in 5 patients with 10 ulcers.[4]
Although a greater improvement was noted in the treated group, the results were calculated
according to the number of ulcers rather than based on individual patients. Leslie reported on a
trial that randomly assigned 18 patients with diabetic foot ulcers to receive either topical
hyperbaric oxygen therapy plus standard wound care or standard wound care alone.[5]
Changes in ulcer size and depth did not differ between the 2 groups. Other studies consist of
anecdotal reports or uncontrolled case series.[6]
SYSTEMIC HYPERBARIC OXYGEN THERAPY (HBOT)
In-home Hyperbaric Oxygen
A position statement from the National Board of Diving & Hyperbaric Medical Technology on
in-home HBOT has been published on the Web site for The Undersea and Hyperbaric
Medicine Society (UHMS).[7] The statement indicates that in-home HBOT “is inherently unsafe
MED14 | 6and cannot be condoned.” This position is based on concern for the safety and well-being of
patients as well as those people in proximity to the HBOT delivery system because in-home
provision of HBOT is likely to:
• Bypass otherwise mandatory federal, state, and local codes related to design, construction,
installation, and operation of these devices; and
• Occur without adequate physician oversight and the operational support of appropriately
qualified HBOT providers.
Acute Coronary Syndromes
Systematic Reviews
A 2012 Cochrane review by Bennett identified 6 trials with a total of 665 patients evaluating
HBO for acute coronary syndrome.[8] All of the studies included patients with acute myocardial
infarction (MI); one study also included individuals presenting with unstable angina.
Additionally, all trials used HBOT as an adjunct to standard care. Control interventions varied;
only 1 trial described using a sham therapy to blind participants to treatment group allocation.
In a pooled analysis of data from 5 trials, there was a significantly lower rate of death in
patients who received HBOT compared to a control intervention (RR: 0.58: 0.36 to 0.92). Due
to variability of outcome reporting in the studies, few other pooled analyses could be
conducted. A pooled analysis of data from 3 trials on improvements in left ventricular function
did not find a statistically significant benefit of HBOT (RR: 0.09; 95% CI: 0.01 to 1.4). The
authors noted that, although there is some evidence from small trials that HBOT is associated
with a lower risk of death, larger trials with high methodologic quality are needed in order to
determine which patients, if any, can be expected to derive benefit from HBOT. Therefore,
HBOT is considered investigational in the treatment of acute coronary syndromes.
Autism Spectrum Disorders (ASD)
Systematic Reviews
A 2016 systematic review on hyperbaric oxygen therapy for treatment of children with autism
identified one RCT[9] with a total of 60 children. The study quality was rated as low using
GRADE criteria with small sample size and wide confidence intervals. The results indicated no
improvement in social interaction and communication, behavioral problems, communication
and linguistic abilities, or cognitive function. The authors reported minor-grade ear barotrauma
as adverse events.
A 2012 systematic review[10] of RCTs on hyperbaric oxygen therapy for treatment of children
with autism identified two RCTs[11, 12]with a total of 89 participants. In both RCTs the active
hyperbaric treatment was 24% oxygen delivered at an atmospheric pressure of 1.3
atmospheres (atm). Although this regimen was referred to as HBOT in the article, it differed
from standard HBOT which uses 100% oxygen and a pressure of at least 1.4 atm. A detailed
analysis of these RCTs is provided below. Briefly, one of the two RCTs found better outcomes
after hyperbaric oxygen compared with placebo treatment, and the other did not find significant
differences in outcomes. The author concluded that additional sham-controlled trials with
rigorous methodology are needed in order to draw conclusions about the efficacy of HBOT for
treating autism.
Randomized Controlled Trials (RCTs)
MED14 | 7The following is a summary of the 2 RCTs reported in the above systematic review:
• One of the above two RCTs was by Rossignol.[11] This study was a double-blind RCT
that included 62 children, ages 2-7, meeting DSM-IV criteria for autistic disorder. The
active treatment was hyperbaric treatment at 1.3 atmospheres (atm) and 24% oxygen in
a hyperbaric chamber. (This regimen differs from standard HBOT which uses 100%
oxygen and a pressure of at least 1.4 atm). The other group received a sham treatment
consisting of 1.03 atm and ambient air (21% oxygen). Both groups received 40 sessions
of active or sham treatment lasting 60 minutes each over a period of 4 weeks. The
equipment, procedures, etc. in the two groups were as similar as possible to maintain
blinding. The investigators, participants, parents, and clinic staff were blinded to
treatment group. Only the hyperbaric technician, who had no role in outcome
assessment, was aware of group assignment. After completion of the 4-week study,
families with children in the control group were offered the active intervention. When
asked at the end of the study, there was no significant difference in the ability of parents
to correctly guess the group assignment of their child.
The outcomes were change compared to baseline after 4 weeks on the following
scales: Aberrant Behavior Checklist (ABC) total score and 5 subscales; Autism
Treatment Evaluation Checklist (ATEC) total score and 4 subscales; and Clinical Global
Impression-Improvement (CGI) overall functioning score and 18 subscales. P values ofstatistically significant outcomes. The Undersea and Hyperbaric Medical Society
(UHMS) issued a position paper after publication of the Rossignol et al. study stating
that they still did not recommend routine treatment of autism with HBOT.[13]
• The other RCT included in the systematic review was a double-blind RCT that began
with 46 children with autism, ages 2-14 years, who were matched in pairs according to
age and the number of hours of Applied Behavior Analysis (ABA) treatment they were
receiving at the start of the study. Randomized[12] treatment allocation of the matched
pairs was by coin toss. Both groups received 80 1-hour sessions of active treatment
(24% oxygen at 1.3 atm) or sham treatment (room air at ambient pressure) for up to 15
weeks. Participants were allowed to undergo ABA, take any supplements,
pharmacological interventions, and dietary modifications. Twelve patients withdrew from
the trial, leaving 18 patients in the treatment group and 16 in the control group.
The primary outcome of change in symptoms was based on direct observation and the
scales noted in the Rossignol et al. study above in addition to the Behavior Rating
Inventory of Executive Functioning (BRIEF), Parent Stress Index (PSI), Peabody Picture
Vocabulary Test (PPVT-III), Repetitive Behavior Scale (RBS), and the Vineland
Adaptive Behavior Scales (VABS-II). Direct observation and intention to treat analysis of
test scores found no significant difference on any outcome measures between the
treatment and sham groups. No participants experienced adverse effects attributable to
barotrauma (e.g., pressure injury to tympanic membranes or sinuses).
A limitation of this study was the small sample size which was determined to be
adequate to detect only large effects, which were not present in this study. In addition,
since some patients in both groups received intensive ABA interventions during the
study period, any potential effects of HBOT could not be isolated. The authors
concluded that the active treatment had no significant beneficial effect on ASD and was
not recommended for the treatment of ASD symptoms.
One additional RCT not included in the systematic review above was identified:
A 2012 RCT published after the systematic review randomly assigned 60 children with
autism to receive 20 one-hour sessions with HBOT or sham air treatment (n=30 per
group).[14] The primary outcome measures were change in the ATEC and CGI,
evaluated separately by clinicians and parents. There were no statistically significant
differences between groups on any of the primary outcomes. For example, post-
treatment clinician-assessed mean scores on the ATEC were 52.4 in the HBOT group
and 52.9 in the sham air group.
Conclusion
There is insufficient evidence from well-designed RCTs that HBOT improves health outcomes
for patients with autism spectrum disorder; therefore, HBOT therapy for this indication is
considered investigational.
Bell’s Palsy
Systematic Review
In 2012, Holland published a Cochrane review evaluating HBOT in adults with Bell’s palsy.[15]
The authors identified one RCT with 79 participants, and this study did not meet the Cochrane
MED14 | 9review methodologic standards because the outcome assessor was not blinded to treatment
allocation. Therefore, the evidence is insufficient to permit conclusions and HBOT is
considered investigational for the treatment of Bell’s palsy.
Randomized Controlled Trials (RCTs)
No RCTs have been published since the 2012 Cochrane review.
Bisphosphonate-related Osteonecrosis of the Jaw (BRONJ)
Randomized Controlled Trials (RCTs)
An unblinded RCT was published by Freiberger in 2012 on use of HBOT as an adjunct
therapy for patients with bisphosphonate-related osteonecrosis of the jaw.[16] Forty-nine
patients were randomly assigned to HBOT in addition to standard care (n=22) or standard
care alone (n=27). Five patients in the standard care group received HBOT and 1 patient
assigned to the HBOT group declined HBOT. The investigators decided to do a per protocol
(PP) analysis (actual treatment received) because of the relatively large degree of crossover.
Participants were evaluated at 3, 6 12 and 18 months. Data were available on 46 patients, 25
received HBOT in addition to standard care and 21 received standard care alone. The
primary outcome measure was change in oral lesion size or number. When change from
baseline to last available follow-up was examined, 17 of 25 (68%) of HBO-treated patients
had improvement in oral lesion size or number compared to 8 of 21 (38%) in the standard
care group, p=0.043. When change from baseline to 6, 12 or 18 months was examined, there
was not a statistically significant difference between groups in the proportion of patients with
improvement. In addition, the proportion of patients who healed completely did not differ
significantly between groups at any time point. This single trial does not report consistent
findings of benefit across outcome measures. It also has a number of methodologic
limitations, e.g., unblinded, cross-over, and analysis performed on a per-protocol basis rather
than intention to treat. A disadvantage of the per-protocol analysis is that randomization is not
preserved, and the two groups may differ on characteristics that affect outcomes. As a result,
this trial is insufficient to conclude that HBOT improves health outcomes for patients with
bisphosphonate-related osteonecrosis of the jaw.
Conclusion
Current evidence is insufficient to determine the safety and efficacy of HBOT in the treatment
of bisphosphonate-related osteonecrosis of the jaw. Therefore, HBOT is considered
investigational for this indication.
Cancer Treatment
Randomized Controlled Trials (RCTs)
In an RCTof 32 patients, Heys found no increase in 5-year survival in patients treated with
HBOT prior to chemotherapy for locally advanced breast carcinoma to increase tumor
vascularity.[17] This approach is being studied since studies in animal models have suggested
that HBOT increases tumor vascularity and thus may make chemotherapy more effective. In a
Cochrane review, Bennett concluded that HBOT given with radiotherapy may be useful in
tumor control; however, the authors expressed caution since significant adverse effects were
common with HBOT and indicated further study would be useful.[18]
MED14 | 10Conclusion
Current evidence is insufficient to determine the safety and efficacy of HBOT in the treatment
of cancer of any type and location. Therefore, HBOT is considered investigational for this
indication.
Cerebral Palsy
Randomized Controlled Trials (RCTs)
• In 2012, Lacey published a double-blind RCT that included 49 children age 3-8 years
with spastic cerebral palsy.[19] Participants were randomized to receive 40 treatments
with either HBOT (n=25) or hyperbaric air to simulate 21% oxygen at room air (n=24).
The primary efficacy outcome was change in the Gross Motor Function Measure
(GMFM-88) global score after the 8-week treatment period. The study was stopped
early due to futility, when an interim analysis indicated that there was less than a 2%
likelihood that a statistically significant difference between groups would be found. At
the time of the interim analysis, there was no significant between-group difference in the
post-treatment GMFM-88 global score (p=0.54).
• In the largest RCT to date, Collet et al. randomly assigned 111 children with cerebral
palsy to 40 treatments over a 2-month period of either HBOT (n=57) or slightly
pressurized room air (n=54).[20] The authors found HBOT and slightly pressurized air
produced similar improvements in both groups for outcomes such as gross motor
function and activities of daily living.
Conclusion
HBOT is considered investigational as a treatment for cerebral palsy because it has not been
shown to provide additional health benefits in this patient population.
Compromised Skin Grafts and Flaps
Systematic Reviews
• In a 2010 Cochrane review, Estes found a lack of high quality evidence regarding HBOT
in the treatment of skin grafts and flaps.[21, 22] The authors found one randomized
controlled trial (RCT) on skin grafts for burn wounds (n=48) which reported significantly
higher graft survival with HBOT, and one RCT on flap grafting (n=135) which reported
no significant differences in graft survival with HBOT compared with dexamethasone or
heparin. However, these data are unreliable due to various methodologic limitations
such as biased analysis, omitted data, and small size.
• In 2006, Friedman published a systematic review of literature on use of HBOT for
treating skin flaps and grafts.[23] No RCTs were found. The authors identified 2
retrospective case series on use of HBOT for clinically compromised skin grafts and
flaps. The series had sample sizes of 65 and 26, respectively; both were published in
the 1980s based on treatment provided in the 1970s and 1980s.
Randomized Controlled Trials (RCTs)
No RCTs have been published since the above systematic reviews.
MED14 | 11Conclusion
Although the study of HBOT for compromised skin grafts and flaps goes back several
decades, the clinical trial data is limited to noncomparative case series and a single
randomized controlled trial. This evidence is insufficient to determine the safety and efficacy of
HBOT in the treatment of compromised skin grafts and flaps. Therefore, HBOT is considered
investigational for these indications.
Carbon Monoxide Poisoning
A 2011 Cochrane review of seven RCTs concluded that the available evidence is insufficient to
determine whether adverse neurologic outcomes in patients with carbon monoxide poisoning
are reduced with HBOT.[24] In 2008, the American College of Emergency Physicians (ACEP)
published a clinical policy on critical issues in carbon monoxide poisoning.[25] Their literature
review indicated there was only level C evidence (preliminary, inconclusive, or conflicting
evidence) for treatment of acute carbon monoxide poisoning. The 2008 UHMS guidelines,
however, list carbon monoxide poisoning as an indication for HBOT.
Two blinded randomized trials were discussed in both the Cochrane and ACEP reviews. One
is a study by Scheinkestel, a double-blind, RCT comparing HBOT with normobaric oxygen in
patients with carbon monoxide poisoning.[26] The authors reported that HBOT did not benefit
patient outcomes of neuropsychologic performance when HBOT was completed and at 1-
month follow-up. This study was limited, however, by a high rate (46%) of patients who were
lost to follow-up. Moreover, the trial has been criticized for administrating 100% normobaric
oxygen for at least 72 hours between treatments, which has been called a toxic dose of
oxygen.[27] The critiques also mention that there was an unusually high rate of neurologic
sequelae after the treatment period, which could be due in part to the high dose of oxygen
and/or the high rate of cognitive dysfunction in the study population (69% were poisoned by
carbon monoxide through suicide attempts).
The other blinded trial, by Weaver, also compared hyperbaric and normobaric oxygen.[28]
Patients received either 3 sessions of HBOT or 1 session of normobaric oxygen plus 2
sessions of exposure to normobaric room air. The primary outcome was the rate of cognitive
sequelae at 6 weeks. Cognitive function was assessed using a battery of neuropsychological
tests. At the 6-week follow-up, the intention- to-treat analysis found that 19 of 76 (25.0%) in the
HBOT group and 35 of 76 (46.1%) in the control group had cognitive sequelae; the difference
was statistically significant (p=0.007). There was a high rate of follow-up at 6 weeks, 147 of
152 (97%) of randomized patients. Enrollment in the study was stopped early because an
interim analysis found HBOT to be effective. A follow-up study, which included 147 patients
from the randomized trial and 75 who had been eligible for the trial but had not enrolled, was
published in 2007.[29] Of the group treated with HBOT (n=75), cognitive sequelae were
identified in 10 of 58 (17%) at 6 months and 9 of 62 (14%) at 12 months. Of the group not
treated with HBOT (n=163), 44 of 146 (30%) at 6 months and 27 of 149 (18%) at 12 months
had cognitive sequelae. (The follow-up rate was higher at 12 months because the investigators
received additional funding for data collection.)
Delayed-Onset Muscle Soreness
Systematic Review
In a 2005 Cochrane review, Bennett concluded that available evidence is insufficient to
demonstrate beneficial outcomes with HBOT for delayed-onset muscle soreness and closed
MED14 | 12soft-tissue injury.[30] It was noted that HBOT possibly even increases pain initially and further studies are needed. Therefore, use of HBOT for this indication is considered investigational. Randomized Controlled Trials (RCTs) No RCTs have been published since the 2005 Cochrane review. Dementia Systematic Review A 2012 Cochrane review identified 1 RCT evaluating HBOT for the treatment of vascular dementia.[31] The 2009 study compared HBOT plus donepezil to donepezil-only in 64 patients. The HBOT and donepezil group had significantly better cognitive function after 12 weeks of treatment, as assessed by the Mini-Mental State Examination. However, the Cochrane investigators judged the trial to be of poor methodologic quality because it was not blinded and the methods of randomization and allocation concealment were not discussed. Randomized Controlled Trials (RCTs) No RCTs have been published since the 2012 Cochrane review. Conclusion The current evidence for HBOT as a treatment of dementias of any cause is limited to a single short-term clinical trial on vascular dementia. This evidence is insufficient to permit conclusions about the safety and efficacy of HBOT on vascular dementia. No other randomized controlled trials were found for HBOT as a treatment of demential from any cause. Due to the lack of sufficient evidence, HBOT is considered investigational for treatment of dementias. Femoral Neck Necrosis, Idiopathic Randomized Controlled Trials (RCTs) In 2010, Camporesi published the results of a double-blind RCT that evaluated HBOT in 20 adult patients with idiopathic unilateral femoral head necrosis.[32] Patients received 30 treatments over 6 weeks with either HBOT at 2.5 ATA (n=10) or a sham treatment consisting of hyperbaric air (n=10). The mean severity of pain on a 0-to-10 scale was significantly lower in the HBOT group than the control group after 30 sessions (p
One quasi-randomized trial and 1 delayed-treatment RCT on HBOT for fibromyalgia were
identified. In 2004, a study by Yildiz included 50 patients with fibromyalgia who had ongoing
symptoms despite medical and physical therapy.[33] On an alternating basis, patients were
assigned to HBOT or a control group. The HBOT consisted of fifteen 90-minute sessions at 2.4
ata (1 session per day, 5 d/wk). The control group breathed room air at 1 ata on the same
schedule. Baseline values on the 3 outcomes were similar in the 2 groups. After the course of
HBOT treatment, the mean (SD) number of tender points were 6.04 (1.18) in the HBO group
and 12.54 (1.10) in the control group. The mean (SD) pain threshold was 1.33 kg (0.12) and
0.84 kg (0.12), respectively, and the mean VAS was 31.54 (8.34) and 55.42 (6.58),
respectively. In the study abstract, the authors stated that there were statistically significant
differences between the HBO and control groups after 15 therapy sessions, but the table
presenting outcomes lacked the notation used to indicate between-group statistical
significance. It is not clear whether the control group actually received a sham intervention that
would minimize any placebo effect ie whether or not the control intervention was delivered in a
hyperbaric chamber. The authors stated that the study was double-blind but did not specify
any details of patient blinding.
In 2015, Efrati published an RCT that included 60 female patients who had fibromyalgia for at
least 2 years and were symptomatic.[34] Patients were randomized to an immediate 2 month
course of HBOT or delayed HBOT after 2 months. The HBOT protocol was forty 90-minute
sessions of 100% oxygen at 2 ata (1 session per day, 5 d/wk). Forty-eight of 60 patients (80%)
completed the study and were included in the analysis. After the initial 2 months, outcomes
including number of tender points, pain threshold, and quality of life (SF-36) were significantly
better in the immediate treatment group compared with the delayed treatment group (which
received no specific intervention during this time). After the delayed treatment group had
undergone HBOT, outcomes were significantly improved compared with scores prior to HBOT
treatment. These findings are consistent with a clinical benefit of HBOT, but also with a
placebo effect. A sham-control is needed to confirm the efficacy of HBOT in the treatment of
fibromyalgia and other conditions where primary end points are pain and other subjective
outcomes.
The above studies were few in number with relatively small sample sizes and had
methodological limitations, e.g., quasi-randomization and no or uncertain sham control for a
condition with subjective outcomes susceptible to a placebo effect. Moreover, the HBO
protocol varied (e.g., 15 HBOT sessions vs 40 HBOT sessions). Thus, the evidence is
insufficient to draw conclusions about the impact of HBOT on health outcomes for patients with
fibromyalgia.
Fracture Healing
Systematic Review
In 2012, Bennett published a Cochrane review on HBOT to promote fracture healing and treat
non-union fractures.[35] The investigators did not identify any published RCTs on this topic that
compared HBOT to no treatment, sham treatment, or another intervention and reported bony
union as an outcome.
Randomized Controlled Trials (RCTs)
No RCTs have been published since the 2012 Cochrane review.
Conclusion
MED14 | 14Due to the lack of RCTs, it is not possible to conclude whether the use HBOT to promote
fracture healing improves outcomes; therefore, the use of HBOT for this indication is
considered investigational.
Headaches
When assessing any treatment focused on pain relief, randomized, placebo-controlled trials
are necessary to investigate the extent of any placebo effect and to determine whether any
improvement with the treatment exceeds that associated with a placebo.
The following is a summary of the available evidence:
Migraine headaches
• Systematic Review
A 2008 Cochrane review by Bennett identified RCTs that evaluated the effectiveness of
systemic hyperbaric oxygen therapy for preventing or treating migraine headache
compared to another treatment or a sham control.[36] Five trials with a total of 103
patients were identified that addressed treatment of acute migraine with HBOT. A
pooled analysis of 3 trials (total of 43 patients) found a statistically significant increase in
the proportion of patients with substantial relief of migraine within 45 minutes of HBOT
(relative risk [RR] 5.97, 95% confidence interval [CI]1.46-24.38, p=0.001). No other
pooled analyses were conducted due to variability in the outcomes reported in the trials.
The meta-analysis did not report data on treatment effectiveness beyond the immediate
post-treatment period, and the methodologic quality of trials was moderate to low, e.g.,
randomization was not well-described in any trial. There was no evidence that HBOT
could prevent episodes of migraine headache.
• Randomized Controlled Trials (RCTs)
In 2004 Eftedal reported the results of a randomized, double-blind, placebo-controlled
trial to assess whether HBOT had a prophylactic effect on migraine headache. [37] Forty
patients were randomly assigned to either a treatment group receiving 3 sessions of
HBOT or a control group receiving 3 hyperbaric treatments with room air. Thirty-four
patients completed the study. Efficacy was measured as the difference between pre-
and post-treatment hours of headache per week. There was no significant reduction in
hours of headache with HBOT compared with hyperbaric air treatments. Nor was there
a significant difference in either group in pre- and post-treatment levels of endothelin-1
in venous blood. The authors concluded that that HBOT had no significant prophylactic
effect on migraine headache or on the endothelin-1 level in venous blood.
Cluster headaches
• Systematic Reviews
Two 2008 systematic reviews, including the Cochrane review noted above, reported few
studies comparing HBOT with sham treatment for cluster headaches.[36, 38] Available
randomized, placebo-controlled trials measuring effect on symptoms are unreliable due
to very small size.[39, 40]
• Randomized Controlled Trials (RCTs)
MED14 | 15No RCTs have been published since the 2008 systematic reviews.
• Conclusion
Due to the lack of sufficient evidence from well-designed clinical trial, HBOT for the
treatment of headaches from any cause is considered investigational.
Herpes Zoster
Randomized Controlled Trial (RCT)
In 2012, Peng published an RCT evaluating HBOT as a treatment of herpes zoster.[41] Sixty-
eight patients with herpes zoster diagnosed within the previous 2 weeks were randomized to
30 sessions of HBOT (n=36) or medication treatment (n=32). Pharmacotherapy included
antiviral, pain, nerve nutritive and antidepressive medication. Therapeutic efficacy was
calculated at the end of the 3-week treatment period and included the proportion of patients
who were healed (i.e., complete subsidence of pain and rash) or improved (i.e., significant
pain relief and rash subsistence). Rates of therapeutic efficacy were 97.2% in the HBOT
group and 81.3% in the medication group (pThere is insufficient evidence that HBOT is effective for treating inflammatory bowel disease.
Only 1 small RCT has been published, and this study did not find a significant improvement in
health outcomes when HBOT was added to standard medical therapy.
In Vitro Fertilization
In a 2005 nonrandomized pilot study, Van Voorhis reported that HBOT was well tolerated in
women undergoing ovarian follicular stimulation for in vitro fertilization; however no outcomes
were reported.[45] Therefore, current evidence is insufficient to permit conclusions and HBOT is
considered investigational for this indication.
Mental Illness
A Rapid Response Report from the Canadian Agency for Drugs and Technologies in Health
(CADTH) searched the literature through July 2014 on the clinical effectiveness of hyperbaric
oxygen therapy for treatment of adults with posttraumatic stress disorder, generalized anxiety
disorder, and/or depression.[46]
The review’s inclusion criteria were health technology assessments, systematic reviews, meta-
analyses, RCTs or nonrandomized studies comparing HBOT to any active treatment and
reporting clinical outcomes. No eligible studies were identified.
Multiple Sclerosis
A Cochrane review of RCTs on HBOT for multiple sclerosis was published by Bennett in
2004.[47] The authors identified 9 RCTs, with a total of 504 participants that compared the
effects of HBOT with placebo or no treatment. The primary outcome of the review was score
on the Expanded Disability Status Scale (EDSS). A pooled analysis of data from 5 trials
(N=271) did not find a significant difference in change in the mean EDSS after 20 HBOT
treatments versus control (mean difference [MD], -0.07; 95% CI, -0.23 to 0.09). Moreover, a
pooled analysis of data from 3 trials (n=163) comparing HBOT and placebo did not find a
significant difference in mean EDSS after 6 months of follow-up (MD = -0.22; 95% CI, -0.54 to
0.09).
Osteomyelitis
No prospective clinical trials on chronic refractory osteomyelitis or acute refractory
osteomyelitis were identified in updated searches. The justification for the use of HBOT in
chronic osteomyelitis has been primarily based on case series. Among the larger case series,
Maynor reviewed the records of all patients with chronic osteomyelitis of the tibia seen at one
institution.[48] Follow-up data were available on 34 patients who had received a mean of 35
adjunctive HBO treatments (range, 6-99). Of the 26 patients with at least 2 years of follow-up
after treatment, 21 (81%) remained drainage-free. Twelve of 15 (80%) with follow-up data at 60
months had remained drainage-free. A study by Davis reviewed outcomes for 38 patients with
chronic refractory osteomyelitis treated at another U.S. institution.[49] Patients received HBOT
until the bone was fully recovered with healthy vascular tissue; this resulted in a mean of 48
daily treatments (range, 8-103). After a mean posttreatment follow-up of 34 months, 34 of 38
(89%) patients remained clinically free of infection (i.e., drainage-free and no tenderness, pain,
or cellulitis). Success rates from several smaller case series, all conducted in Taiwan, are 12 of
13 (92%) patients, 11 of 14 (79%) patients, and 13 of 15 (86%) patients.[50-52] A high
percentage of refractory patients in these series had successful outcomes.
MED14 | 17Radiotherapy Adverse Effects
Systematic Review
• A 2017 systematic review on the effectiveness of HBOT for the treatment of radiation-
induced skin necrosis included eight articles with five case series studies, two case
reports, and one observational cohort.[53] The authors investigated the change in
symptoms and alteration in wound healing and reported that HBOT was a safe
intervention with promising outcomes. However, the authors recommended additional
high quality evidence in order for HBOT to be considered as a relevant treatment for this
indication. s
• A 2014 systematic review on the safety and effectiveness of HBOT for the treatment of
non-neurological soft tissue radiation-related injuries (STRI) included 41 articles, 11 of
which compared regimens with and without HBOT.[54] Serious adverse effects were rare
and the more common adverse effects were minor and self-limiting. Evidence of a
beneficial effect of HBOT was reported radiation proctitis and STRI of the head and
neck, but not for post-radiation soft tissue edema or radiation cystitis. The authors
recommended further studies to validate the use of HBOT as both a definitive and
adjunctive treatment for individual STRI.
• In 2010, Spiegelberg conducted a systematic review of studies on HBOT to prevent or
treat radiotherapy-induced head and neck injuries associated with treatment of
malignant tumors.[55] The authors identified 20 studies. Eight of the studies included
control groups; their sample sizes ranged from 19 to 78 individuals. Four (50%) of the
studies with a control group concluded that HBOT was effective, and the other 4 did not
conclude that the HBOT was effective. The authors noted a paucity of RCTs but did not
state the number of RCTs identified in their review.
Randomized Controlled Trials
• Teguh reported on 17 patients with oropharyngeal or nasopharyngeal cancer who were
treated with radiation therapy.[56] Eight patients were randomly assigned to receive 30
sessions of HBOT, beginning within 2 days of completing radiation therapy, and 9
patients received no additional treatment. All patients were included in the analysis.
Quality of life outcomes were assessed and the primary outcome was specified as
xerostomia at 1 year. Quality of life measures did not differ significantly between groups
in the acute phase (first 3 months). For example, 1 month after treatment, the mean
visual analog scale (VAS) score for xerostomia (0-to-10 scale) was 5 in the HBOT group
and 6 in the control group. However, at 1 year, there was a statistically significant
difference between groups; the mean VAS score for xerostomia was 4 in the HBOT
group and 7 in the control group (p=0.002). Also at 1 year, the mean quality of life score
for swallowing (0-to-100 scale) was 7 in the HBOT group and 40 in the control group
(p=0.0001). The study is limited by the small sample size and the wide fluctuation over
the follow-up period in quality-of-life ratings.
• In 2010, Gothard randomized 58 patients with arm lymphedema (at least 15% increase
in arm volume) following cancer treatment in a 2:1 ratio to receive HBOT (n=38) or
usual care without HBOT (n=20).[57] Fifty-three patients had baseline assessments and
46/58 (79%) had 12-month assessments. No statistically significant difference was
found in the change in arm volume from baseline to 12-month follow-up. The median
MED14 | 18change from baseline was -2.9% in the treatment group and -0.3% in the control group.
The study protocol defined response as at least an 8% reduction in arm volume relative
to the contralateral arm. According to this definition, 9 of 30 (30%) patients in the HBOT
group were considered responders compared with 3 of 16 (19%) in the control group;
the difference between groups was not statistically significant. Other outcomes, e.g.,
quality-of-life scores on the Short-Form (SF)-36, were also similar between groups.
Conclusion
Due to the lack of sufficient evidence from well-designed clinical trial, HBOT for the treatment
of adverse effects related to radiation therapy is considered investigational.
Radionecrosis and Osteoradionecrosis
Several systematic reviews of RCTs have been published. A 2008 Cochrane review by
Esposito reviewed the use of HBOT in patients requiring dental implants.[29] The authors
identified 1 randomized trial involving 26 patients. The authors concluded that despite the
limited amount of clinical research available, it appears that HBOT in irradiated patients
requiring dental implants may not offer any appreciable clinical benefits. They indicated that
there is a need for more RCTs to ascertain the effectiveness of HBOT in irradiated patients
requiring dental implants.
In 2012, Bennett published a Cochrane review on HBOT for late radiation tissue injury.[58] The
authors identified 11 RCTs; there was variability among trials, and study findings were not
pooled for the primary outcomes of survival, complete resolution of necrosis or tissue damage,
and improvement in a late effects symptom scale. In a pooled analysis of 3 studies, a
significantly higher proportion of patients with osteoradionecrosis achieved complete mucosal
cover after HBOT compared with controls (RR=1.30; 95% CI, 1.09 to 1.55). From their review
of the literature, the authors concluded that data from small trials “suggest that for people with
LRTI [late radiation tissue injury] affecting the head, neck, anus, and rectum, [HBOT] is
associated with improved outcome. HBOT also appears to reduce the chance of ORN
[osteoradionecrosis] following tooth extraction in an irradiated field. There was no such
evidence of any important clinical effect on neurological tissues. The application of HBOT to
selected patients and tissues may be justified.”
Stroke
Current evidence is insufficient to permit conclusions about whether HBOT improves health
outcomes in the treatment of stroke or stoke-related functional limitations. The following is a
summary of the available evidence:
Acute Stroke
• Systematic Reviews
o In a 2005 Cochrane systematic review, Bennett evaluated HBOT for acute stroke.[59]
The investigators identified 6 RCTs with a total of 283 participants that compared HBOT
to sham HBOT or no treatment. The authors were only able to pool study findings for 1
outcome, the mortality rate at 3-6 months. A pooled analysis of 3 trials found no
significant benefit of HBOT compared to the control for this outcome. Based on the
available evidence, acute ischemic stroke is considered investigational
MED14 | 19o In a 2005 systematic review, Carson concluded that current evidence did not
demonstrate any benefit with the use of HBOT for the treatment of stroke.[60] The
authors noted it was undetermined whether there were any benefits with HBOT that
would outweigh potential harms, and further study was required.
o In a 2014 update of a Cochrane systematic review, Bennett evaluated HBOT for acute
ischemic stroke. The investigators identified 11 RCTs with a total of 705 participants
that compared HBOT with sham HBOT or no treatment. The authors were only able to
pool study findings for 1 outcome; mortality at 3 to 6 months. A pooled analysis of data
from 4 trials with a total of 106 participants did not find a significant benefit of HBOT
compared with a control condition for this outcome (RR=0.97; 95% CI, 0.34 to 2.75).
• Randomized Controlled Trials (RCTs)
No RCTs have been published since the 2005 systematic reviews.
Stroke-related motor dysfunction
• Randomized Controlled Trials (RCTs)
In 2013, Efrati published an RCT evaluating HBOT for treatment of neurologic
deficiencies associated with a history of stroke.[61] The study included 74 patients with
at least one motor dysfunction who had an ischemic or hemorrhagic stroke 6-36
months prior to study participation. Participants were randomly assigned to receive 2
months of HBOT (40 daily sessions, 5 days per week, n=30) or delayed treatment
(n=32). Patients were evaluated at baseline and 2 months. For patients in the delayed
treatment control group, outcomes were evaluated at 4 months after crossing over and
receiving HBOT. Twenty-nine of 32 patients (91%) in the delayed treatment group
crossed over to the active intervention. Outcome measures included the National
Institutes of Health Stroke Scale (NIHSS), which was measured by physicians blinded
to treatment group, and several patient-reported quality-of-life and functional status
measures.
At 2 months’ follow-up, there was statistically significantly greater improvement in
function in the HBOT group compared to the control group as measured by the NIHSS,
quality-of-life scales and the ability to perform activities of daily living (ADLs). These
differences in outcome measures were accompanied by improvements in single-
photon emission computed tomography (SPECT) imaging in the regions affected by
stroke. For the delayed treatment control group, there was a statistically significant
improvement in function after HBOT compared to before treatment. This RCT raises
the possibility that HBOT may induce improvements in function and quality of life for
post-stroke patients with motor deficits. However, the results are not definitive for a
number of reasons. This RCT is small and enrolled a heterogeneous group of post-
stroke patients. The study was not double-blind and the majority of outcome measures,
except for the NIHSS, were patient reported and thus prone to the placebo effect. Also,
there was a high total dropout rate of 20% at the 2-month follow-up point. Therefore,
larger, double-blind studies with longer follow-up are needed to corroborate these
results. Because of these limitations in the evidence, HBOT is considered
investigational for treating motor dysfunction associated with stroke.
Traumatic Brain Injury
MED14 | 20Systematic Review
The systematic review and pooled analysis by Hart (2019) evaluated HBOT for mild traumatic
brain injury (mTBI) associated post-concussive symptoms (PCS) and posttraumatic stress
disorder (PTSD).[62] Data were aggregated from four Department of Defense (DoD) studies
that included participant level data on 254 patients assigned to either HBOT or sham
intervention. An additional three studies with summary-level participant data were summarized
(N=135). The authors assessed changes from baseline to post-intervention on PCS, PTSD,
and neuropsychological measures. The DoD data analyses indicated improvements with
HBOT for PCS, measured by the Rivermead Total Score. Statistically significant improvements
were seen for PTSD based on the PTSD Checklist Total Score, as well as for verbal memory
based on CVLT-II Trial 1-5 Free Recall.
A 2016 meta-analysis by Wang (2016) assessed HBOT for TBI including eight studies with 519
participants that met the eligibility criteria.[63] HBOT protocols varied across studies in the
levels of oxygen and the length and frequency of treatments. The primary outcome was
change in the Glasgow Coma Scale score. A pooled analysis of two studies found a
significantly greater improvement in the mean Glasgow Coma Scale score in the HBOT group
compared with control groups. Mortality (a secondary outcome) was reported in 3 of the 8
studies. Pooled analysis of these 3 studies found a significantly lower overall mortality rate in
the HBOT group than in the control group.
A 2012 Cochrane systematic review addressed HBOT as adjunctive treatment for traumatic
brain injury.[64] The investigators identified 7 RCTs with a total of 571 participants comparing a
standard intensive treatment regimen to the same treatment regimen with the addition of
HBOT. The review did not include studies in which interventions occurred in a specialized
acute care setting. The HBOT regimens varied among studies; for example, the total number
of individual sessions varied from 3 to 30-40. No trial used sham treatment or blinded the staff
members who were treating the patients, and only 1 had blinding of outcome assessment.
Allocation concealment was inadequate in all of the studies. The primary outcomes of the
review were mortality and functional outcomes. A pooled analysis of data from 4 trials that
reported this outcome found a statistically significantly greater reduction in mortality when
HBOT was added to a standard treatment regimen. However, when data from the 4 trials
were pooled, the difference in the proportion of patients with an unfavorable functional
outcome at final follow-up did not reach statistical significance. Unfavorable outcome was
commonly defined as a Glasgow Outcome Score (GOS) of 1, 2 or 3, which are described as
‘dead’, ‘vegetative state’ or ‘severely disabled’. Studies were generally small and were judged
to have substantial risk of bias.
Randomized Controlled Trials
A 2012 sham-controlled double-blind trial evaluating HBOT was published after the 2012
Cochrane review.[65] The study included 50 military service members, 48 of whom were male,
with combat-related mild traumatic brain injury. Participants were randomized to 30 sessions
of HBOT over 8 weeks (n=25) or a sham intervention (room air at 1.3 ATA) (n=25). The
primary outcome measures were scores on the Immediate Post-Concussive Assessment and
Cognitive Testing (ImPACT) and Post-Traumatic Disorder Check List- Military Version (PCL-
M) instruments. Patients were evaluated after every 5 treatment sessions and at 6 weeks
post-exposure. Forty-eight of 50 participants (96%) completed the study. There were no
statistically significant differences on the ImPACT total mean score or the PCL-M composite
MED14 | 21You can also read
